Large quantities of IgG are transported into female genital tract mucus secretions by the MHC class I-related neonatal Fc receptor (Li et al., Proc. Natl. Acad. Sci. U.S.A. 108:4388 (2011), resulting in at least ten-fold more IgG than IgA (Usala et al., J. Reprod. Med. 34:292 (1989)). However, despite this predominance of IgG, the precise mechanism(s) by which secreted IgG can prevent vaginal infections are not well understood. Previous animal studies have shown that antibodies (Ab) can provide robust protection against vaginal challenge with pathogens, including human immunodeficiency virus (HIV) and herpes simplex virus-2 (HSV-2), when applied intravaginally (Burton et al., Proc. Natl. Acad. Sci. U.S.A. 108:11181 (2011); Sherwood et al., Nature Biotechnol. 14:468 (1996); Veazey et al., Nature Med. 9:343 (2003); Whaley et al., J. Infect. Dis, 169:647 (1994)) or even intravenously (Hessell et al., PLoS Pathogens 5:e1000433 (2009); Mascola et al., Nature Med. 6:207 (2000)). Many investigators have focused on neutralizing Ab, which, at sufficiently high doses, provided sterilizing immunity against simian-human immunodeficiency virus (SHIV) challenge in rhesus macaques (Burton et al., Proc. Natl. Acad. Sci. U.S.A. 108:11181 (2011)). In the same studies, non-neutralizing or poorly neutralizing Ab provided at best only partial protection, with some infected animals exhibiting reduced viral load. Studies by Hessell et al. and Mascola et al. showed complete protection in some animals even by weakly neutralizing antibodies, as well as reduced viremia in others (Hessell et al., PLoS Pathogens 5:e1000433 (2009); Mascola et al., Nature Med. 6:207 (2000)).
Few studies have explored the potential protective role of IgG within the mucus secretions overlaying the epithelial tissue, which sexually transmitted viruses invariably encounter and must penetrate in order to reach target cells. Well-known Ab effector functions in blood and lymph (e.g., complement activation, opsonization, and ADCC) are absent or limited in healthy female genital secretions, which typically have little complement activity and few if any active leukocytes (Cone, In Handbook of Mucosal Immunology. P. L. Ogra et al., editors. Academic Press, San Diego, Calif. 43-64 (1999); Hill et al., Am. J. Obstet. Gynecol. 166:720 (1992); Schumacher, Hum. Reprod. 3:289 (1988)). These classical mechanisms of systemic immune protection do not adequately account for the moderate but significant protection observed in the landmark Thai RV144 HIV vaccine trial (Kresge, IAVI Report Vol 13, Number 5 (2009); Rerks-Ngarm et al., N. Engl. J. Med. 361:2209 (2009)). The vaccination regimen modestly reduced the risk of HIV acquisition despite inducing primarily non-neutralizing Ab and otherwise offering little to no protection against systemic progression of infections once acquired, suggesting that protection likely occurred prior to initiation of infection. A better understanding of potential additional mechanisms of vaginal mucosal immunity will also likely be critical for developing effective vaccines against other sexually transmitted infections, including HSV, which has been shown to evade complement and other classical antibody-mediated protective mechanisms (Brockman et al., Vaccine 26 Suppl 8:194 (2008); Hook et al., J. Virol. 80:4038 (2006); Lubinski et al., J. Exp. Med. 190:1637 (1999)). To date, herpes vaccine candidates have achieved only transient and partial protection despite inducing high neutralizing serum antibody titers and cellular immunity (Chentoufi et al., Clin. Dev. Immunol. 2012:187585 (2012)). A Phase III clinical trial, using a subunit vaccine based on HSV-2 glycoprotein D, demonstrated some protection against HSV-1 infection but no efficacy against HSV-2 infection and no overall efficacy against genital disease (Belshe et al., New Eng. J. Med. 366:34 (2012)).
There is a need in the art for new compositions, and methods of using such compositions, to prevent and treat infectious diseases and provide contraception.